A collection of 119 strains of Mycobacterium tuberculosis isolated from patients with pulmonary tuberculosis in the Archangel Oblast, Russia, in 1998 and 1999 were studied by using restriction fragment length polymorphism (RFLP) analysis with the IS6110 probe and spoligotyping. Resistance of the strains to antituberculosis drugs was analyzed by the BACTEC method, and mutations associated with rifampin resistance were detected by using the Inno-LiPA Rif. TB test. RFLP analysis and spoligotyping demonstrated that 53 (44.5%) of the strains belonged to the Beijing genotype. These strains showed a significantly higher rate of resistance than M. tuberculosis strains of other genotypes circulating in the region. In particular, 43.4% of the strains of the Beijing genotype were multidrug resistant; in contrast, only 10.6% of the other strains were. Of the strains of the Beijing genotype, 92.5% were part of a cluster, while only 33.3% of the remaining strains were clustered. Analysis of the medical records of the patients demonstrated that individuals infected with a strain of the Beijing genotype were significantly more likely to be alcohol abusers and to have chronic obstructive pulmonary disease prior to the tuberculosis diagnosis. Multivariate analysis showed that both variables were independently associated with infection by strains belonging to the Beijing genotype. Our study demonstrated that strains of the Beijing genotype are an important cause of tuberculosis in the Archangel Oblast and that dissemination of these strains is associated with the high incidence of drug resistance.

Extensively drug-resistant tuberculosis (XDR-TB) is present in all regions and poses serious challenges for public health and clinical management. Laboratory diagnosis is difficult and little evidence exists to guide clinicians in treating people with XDR-TB effectively. To summarise the available data on diagnosis and treatment, the current authors performed a systematic review on 13 recent studies of the epidemiology and clinical management of XDR-TB.Studies that met inclusion criteria were reviewed, in order to assess methodology, treatment regimens and treatment outcomes.Meta-analysis of currently available data is not possible because of inconsistent definitions and methodologies. Data show that XDR-TB can be successfully treated in up to 65% of patients, particularly those who are not co-infected with HIV. However, treatment duration is longer and outcomes are in general poorer than for non-XDR TB patients.To strengthen the evidence for extensively drug-resistant tuberculosis diagnosis, treatment and prevention, future studies should: 1) be prospective in design; 2) adopt standardised, internationally accepted definitions; 3) use quality-assured laboratory testing for all first-and second-line drugs; and 4) collect data on an agreed-upon set of standard variables, allowing for comparisons across studies. Early diagnosis and aggressive management of extensively drugresistant tuberculosis provide the best chance of positive outcome, but prevention is still paramount.KEYWORDS: Extensively drug-resistant tuberculosis, microbiological diagnosis, outcomes, systematic review, treatment efficacy A ccording to the latest World Health Organization (WHO) estimates, approximately 9.2 million new cases of tuberculosis (TB) and 1.5 million TB-related deaths occurred in 2006. TB remains a global emergency [1]. TB treatment requires multiple antibiotics over 6 months or more to achieve cure but, for decades, no new and better drugs have been developed and licensed. In addition, drug-resistant strains of Mycobacterium tuberculosis have emerged as a serious problem. The prevalence of multidrugresistant (MDR) M. tuberculosis (defined as in vitro resistance to isoniazid and rifampicin, the two most potent first-line drugs for TB treatment) is now widely reported [2,3]. MDR strains are currently found in more than 15% of all new cases of TB in some areas of the former Soviet Union (Azerbaijan, Moldova, Ukraine and Tomsk Oblast (Russian Federation)), and in more than 10% in parts of China and other areas of the former Soviet Union (Latvia, Estonia, Kazakhstan, Uzbekistan, and Ivanovo and Mari El (both Russian Federation)) [4][5][6].Strains of M. tuberculosis resistant to second-line drugs are also emerging. Cases of extensively drug-resistant (XDR)-TB (defined as in vitro drug resistance to isoniazid and rifampicin plus any fluoroquinolone and at least one of the injectable drugs (capreomycin, kanamycin or amikacin)) have been described around the globe [7,8] Despite the growing amount of public awareness about TB dru...

Currently, no information is available on the effect of resistance/susceptibility to first-line drugs different from isoniazid and rifampicin in determining the outcome of extensively drug-resistant tuberculosis (XDR-TB) patients, and whether being XDR-TB is a more accurate indicator of poor clinical outcome than being resistant to all first-line anti-tuberculosis (TB) drugs.To investigate this issue, a large series of multidrug-resistant TB (MDR-TB) and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation during the period 1999-2006 were analysed. Drug-susceptibility testing for first-and second-line anti-TB drugs, quality assurance and treatment delivery was performed according to World Health Organization recommendations in all study sites.Out of 4,583 culture-positive TB cases analysed, 361 (7.9%) were MDR and 64 (1.4%) were XDR. XDR-TB cases had a relative risk (RR) of 1.58 to have an unfavourable outcome compared with MDR-TB cases resistant to all first-line drugs (isoniazid, rifampicin ethambutol, streptomycin and, when tested, pyrazinamide), and an RR of 2.61 compared with ''other'' MDR-TB cases (those susceptible to at least one first-line anti-TB drug among ethambutol, pyrazinamide and streptomycin, regardless of resistance to the second-line drugs not defining XDR-TB).The emergence of extensively drug-resistant tuberculosis confirms that problems in tuberculosis management are still present in Europe. While waiting for new tools which will facilitate management of extensively drug-resistant tuberculosis, accessibility to quality diagnostic and treatment services should be urgently ensured and adequate public health policies should be rapidly implemented to prevent further development of drug resistance.

Prisons play a significant role in the epidemiology of drug-resistant tuberculosis. A total of 114 Mycobacterium tuberculosis isolates recovered from patients in the Archangel prison (Archangel, Russia) in 2001 were studied using restriction fragment-length polymorphism analysis and spoligotyping. Drug susceptibility was analyzed by the radiometric broth method (BACTEC; Becton Dickinson Diagnostic Systems). According to genotyping studies, 87 (76.3%) of the isolates belonged to the W-Beijing family. Nearly all (96.6%) W-Beijing isolates were part of a cluster, whereas only 25.9% of the other isolates were clustered (P<.001). The largest cluster comprised 43 patients. Multidrug resistance was high among new (34.0%) and previously treated (55.0%) cases. Resistance to ethambutol (OR, 3.4; 95% CI, 1.0-12.7; P=.03) and streptomycin (OR, 4.2; 95% CI, 1.5-11.6; P=.001) was significantly associated with infection with W-Beijing isolates. Tuberculosis due to drug-resistant W-Beijing isolates is a major problem in the Archangel prison.